• Journal of Food Hygiene and Safety
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• v.15 no.1
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• pp.30-35
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• 2000

To investigate the effects of bacterial endotoxin on lipids and cytokines, and to explain the relationships between their changes, we carried out this study using experi-mentally Escherichia coli (E. coli) endotoxin-induced septicemic rabbits. The triglyceride and cholesterol concentrations in endotoxin groups were generally high (p<0.01 or 0.05) at all sampling time points (from 3hr to 24 hr), while phospholipid concentrations in endotoxin groups elevated in dose-dependent fashion at 3hr and 6hr after endotoxin injection compared to control group (p<0.05), There were significant negative correlations between lipids changes and cytokines (TNF-$\alpha$ and IL-1$\beta$) each other (p<0.05), and endotoxic rabbits having higher triglyceride of cholesterol levels shown relatively better conditions compared with others. As a result, the alterations in the lipid compositions caused by endotoxin may imply an active exhibition of the host defense mechanism rather than the disturbances of lipid metabolism.

• BMB Reports
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• v.29 no.6
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• pp.530-534
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• 1996

Astrocyte are the major glial cell type in the central nervous system (CNS), and analogous to macrophage, mediates the number of immune responses such as production of cytokines including tumor necrosis factor alpha ($TNF-{\alpha}$) upon activation. $TNF-{\alpha}$ has been implicated in neuroimmunological disorders through killing oligodendrocytes and thus causing demyelination. It has been previously demonstrated that mitogen-activated T cells synthesized a 26 kDa precursor form of $TNF-{\alpha}$ which is bound to the surface of a membrane, and is later secreted as a 17 kDa mature version. In order to examine whether astrocytes would produce the transmembrane form of $TNF-{\alpha}$, astrocytes were stimulated with biological stimuli and the membrane form of $TNF-{\alpha}$ was analyzed by Western blot and FACS analysis. When astrocytes are stimulated with lipopolysaccharide (LPS), $IFN-{\gamma}/LPS$, or $IFN-{\gamma}/IL-1{\beta}$, they were able to express a membrane-anchored $TNF-{\alpha}$ of approximately 26 kDa protein which was immunoreactive to an $anti-TNF-{\alpha}$ antibody, whereas unstimulated astrocytes or astrocytes treated with $IFN-{\gamma}$ or $IL-1{\beta}$ alone was not. Our FACS data were also consistent with the immunoblot analysis. Our result suggests that the membrane form of $TNF-{\alpha}$ expressed by activated astrocytes may cause local damage to oligodendrocytes by direct cell-cell contact and contribute to demyelination observed in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE).

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.12
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• pp.1800-1806
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• 2008

Cytokines play a central role in the mucosal immune response and are involved in regulation of nutrient absorption, metabolism and animal growth. This study investigated the effect of diet manipulation with specialized protein or peptide sources on expression of cytokine (IL-1, IL-6, IL-10, and TNF-${\alpha}$) mRNA abundance in different intestinal regions and at different ages post-weaning in piglets. A total of 48 (17 days of age, $6.16{\pm}0.34kg\;BW$) weanling pigs were fed either a corn-soy/whey protein basal diet, the basal diet supplemented with spray-dried plasma protein (SDPP), or the basal diet supplemented with $Peptiva^{(R)}$, a hydrolyzed marine plant protein. A fourth treatment group was fed the SDPP diet, but the feed intake level was limited (SDPP-LF). Pigs were killed at 3 and 10 d, and intestinal cytokine mRNA was measured by real-time PCR using the relative quantification method. The SDPP-LF group exhibited an increased TNF-${\alpha}$ mRNA abundance compared with the ad libitum SDPP group (p<0.05). The TNF-${\alpha}$ and IL-10 mRNA abundance increased from the proximal to distal part of the intestine, and the mRNA abundance was greater (p<0.01) in the distal intestine as compared with the proximal and middle intestine. The cytokines IL-1-${\beta}$, IL-10 and TNF-${\alpha}$ mRNA abundance also increased from d3 to d10 postweaning (p<0.01). In summary, restricted feeding increased the TNF-${\alpha}$ mRNA abundance in the small intestine, however neither SDPP nor peptide supplementation affected cytokine mRNA expression. Abundance of mRNA for most cytokines examined in this study increased with age post-weaning, suggesting that during 10 d after weaning the mucosal immune system is still under development.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.26 no.1
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• pp.50-62
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• 2013

Objective : Propionibacterium acnes (P. acnes) is a major pathogenic bacteria for acne vulgaris. This study was performed to evaluate the effects of Lithospermum erythrorhizon extracts on the inflammatory cytokines gene expression by P. acnes in human keratinocytes, HaCaT cell line. Methods : Anti-bacterial activity and cytotoxicity of LE extracts was analyzed by agar plate culture and XTT assay. The cytokines gene expressions were assessed by real time RT-PCR for IL-8, MCP-1 and TNF-${\alpha}$. During the cell culture and treatments, amounts of secreted TNF-${\alpha}$ were measured by ELISA. Translocation of transcription factor NF-${\kappa}B$ from cytoplasm into nucleus was observed by immunocytochemistry and confocal microscopy. Results : There were no anti-bacterial effects and cytotoxicity as high as $1,000{\mu}g/ml$ of LE extracts in XTT assay. Transcription levels of inflammatory cytokines, IL-8, MCP-1 and TNF-${\alpha}$ were increased by P. acnes in HaCaT. LE extracts decreased the upregulated gene transcription levels. However, amounts of secreted TNF-${\alpha}$ were similar in HaCaT cells with P. acnes and LE extracts. Translocation of NF-${\kappa}B$ into nucleus by P. acnes was significantly inhibited by LE extracts. Conclusions : From the results of this study, LE extracts have anti-inflammatory effects on HaCaT cells by P. acnes that decreased the mRNA expressions of IL-8, MCP-1 and TNF-${\alpha}$. This anti-inflammatory effects of LE extracts could provide the potential of therapeutic substance for acne vulgaris.

• Korean Journal of Pharmacognosy
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• v.42 no.3
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• pp.253-259
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• 2011

Macrophages play a vital role in the innate immune system involving defensive cytokines such as TNF (tumor necrosis factor)-${\alpha}$ and nitric oxide (NO). Therefore, we try to elucidate the anti-inflammatory activity of Chaga mushroom (Inonotus Obliquus, IO) in murine macrophages. Raw 264.7 cells and peritoneal macrophages of mice were cultured with or without LPS/LPS + IFN-${\gamma}$ in the presence of IO aqueous extracts (IOE 0.2, 2, 20, 100 ${\mu}g$/mL) for 24 hr and 48 hr, respectively. Exposure of IOE caused the decrease of NO production and increase of TNF-${\alpha}$ production in dose-dependent manner in activated peritoneal macrophage in vitro. To further investigate anti-inflammatory effects of IO ex vivo, we orally administrated capsaicin (PC, 3 mg/kg/day) and IOE (100, 200, 400 mg/kg/day) for 4 consecutive days to C57BL/6 mice (7~9 weeks old, female), then observed the NO secretion and cytokine (TNF-${\alpha}$) production of LPS/LPS + INF-${\gamma}$-stimulated peritoneal macrophages. IOE inhibits NO secretion in dose-dependent manner both ex vivo and in vitro and increases the production of TNF-${\alpha}$ in vitro. In addition, we found that IOE possessed suppressive effects of LPS-stimulated TNF-${\alpha}$, IL-$1{\beta}$, COX-2, as well as iNOS expressions in Raw 264.7 cells. These findings indicate that IOE suppress not only the LPS-induced NO overproduction of murine peritoneal macrophages, but also iNOS, COX-2, TNF-${\alpha}$, and IL-$1{\beta}$ overexpression of LPS-induced Raw 264.7 cells. Consequently, our results suggest that IO may have the anti-inflammatory effects via suppression of the inflammatory cytokines and mediators, and be useful for the treatment of inflammatory diseases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.41 no.4
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• pp.171-175
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• 2015

Objectives: The objective of this study was to identify salivary and serum concentrations of interleukin (IL)-8, IL-6, and tumor necrosis factor alpha ($TNF-{\alpha}$) in patients with oral lichen planus, oral leukoplakia, oral submucous fibrosis, and healthy controls. Materials and Methods: Patients selected included 54 oral lichen planus (41 to 65 years), 50 oral leukoplakia (42 to 65 years), 51 oral submucous fibrosis (41 to 65 years), and 50 healthy controls (42 to 65 years). Oral lichen planus, oral leukoplakia, and oral submucous fibrosis cases were diagnosed using histopathological analysis. Salivary and serum cytokine concentrations were measured using enzyme-linked immunoassay kits in all subjects. Results: The levels of serum and salivary $TNF-{\alpha}$, IL-6, and IL-8 were statistically significantly increased in oral leukoplakia, submucous fibrosis, and lichen planus in contrast to normal healthy subjects (P<0.05). Serum and salivary correlation analysis revealed strong and highly significant correlations for $TNF-{\alpha}$, IL-6, and IL-8 in all groups (r=0.72-0.82, P<0.05). Conclusion: Salivary and serum cytokines were also elevated when analyzed in oral precancerous lesions. Thus, salivary and serum IL-8, IL-6, and TNF-${\alpha}$ levels might act as diagnostic markers for detection of oral precancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.127-134
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• 2009

In the present study, we investigated the anti-allergic effect of the water extract of Bopyeoyangyeong-jun(BYJ) to cytokines and transcription. To investigate the biological effect of BYJ, We examined cytotoxicity and inflammatory cytokine secretion with RBL-2H3. We examined tumor necrosis factor-alpha(TNF-$\alpha$), interleukin(IL)-4 secretion from RBL-2H3 cell after pre- treatment with Bopyeoyangyeong-jun of $1\;mg/m{\ell}$, $2\;mg/m{\ell}$. RBL-2H3 cell was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. We observed that Bopyeoyangyeong-jun reduced TNF-$\alpha$, IL-4 secretion and mRNA expression in RBL-2H3 cells. Moreover, the expression of levels of cyclooxygenase (COX)-2 mRNA, nuclear factor-kappa B (NF-${\kappa}B$) (p65) protein, ERK MAPK, and the degradation of level inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) were down-regulated by BYJ. Taken together, these results indicate that Bopyeoyangyeong-jun hascontrols TNF-$\alpha$, IL-4 secretion on allergic reaction.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.1-12
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• 1999

Bacterial infection of the pulp results in the development of a periapical lesion with the concomitant resorption of periapical bone. The cytokines are believed to play an important role in this matter. The purpose of this study was to find the relationship among the presence of black pigmented bacteria, the levels of cytokines(TNF-${\alpha}$, -${\beta}$, IL-$1{\beta}$, and TGF-${\beta}1$), and the amount of bone resorption in periapical and pulpal diseases. For the purpose, the patients were grouped into chronic apical pathosis, acute apical pathosis, acute pulpitis, and a healthy control group. Root canal samples were taken from periapical tissue exudates during routine endodontic treatment, and the venous blood was taken from each patients. The samples were processed to measure local and systemic levels of the cytokines using enzyme linked immunosorbent assay(ELISA). Bacterial content of Porphyromonas endodontalis, Porphyromonas gingivalis, and Prevotella nigrescens were measured by indirect immunofluorescence method and the size of the periapical lesions were measured from the radiographs. The following results were obtained: 1. The levels of bone resorptive cytokines(TNF-${\alpha}$, TNF-${\beta}$, and IL-$1{\beta}$) in exudates from acute and chronic apical pathoses were significantly higher than those from acute pulpitis and the normal pulps(p<0.05). 2. IL-$1{\beta}$ were the highest among the bone resorptive cytokines in apical pathoses. However, no statistical difference between acute and chronic lesions were found(p>0.05). 3. The levels of TGF-${\beta}1$ in exudates from acute pulpitis and chronic apical pathoses were significantly higher than those from acute apical pathoses and the normal pulps(p<0.05). However, there were no significant correlations among the levels of bone resorptive cytokines. 4. The levels of TNF-${\beta}$ in serum were significantly higher than those from the exudates while serum TGF-${\beta}1$ concentrations were significantly lower(p<0.05). 5. Exudates from the canals in which the P. nigrescens were detected showed significantly higher levels of IL-$1{\beta}$ than those from the canals without the microorganism(p<0.05). 6. There were no significant correlations among the levels of the cytokines, the amount of bone destruction, and the presence of acute and chronic symptoms(p>0.05).

• Korean Journal of Pharmacognosy
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• v.25 no.2
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• pp.132-139
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• 1994

To investigate the effect of Korean mistletoe on stimulation of macrophage, the activity to induce interleukine-1(IL-1) and tumor necrosis factors-${\alpha}(TNF-{\alpha})$ from murine peritoneal macrophage by its extracts originated from oak was examined. From in vitro analysis of the cytokines using the culture supernatants of macrophages stimulated with its extracts for 1hr, it was found that Korean mistletoe induces IL-1 and $TNF-{\alpha}$ from murine macrophage. Furthermore, both extracts of Korean mistletoes that were extracted with distilled water and 2% acetic acid exhibited a significant activity to induce two cytokines. In the stimulation for 30 min, Korean mistletoe at concentration of $1{\sim}100\;\mu/ml$ showed a significant induction of IL-1 from macrophage until 24 hrs after stimulation, showing maximal activity on $5{\sim}10\;hrs\;at\;10{\sim}100\;\mu/ml$. On the other hand, $TNF-{\alpha}$ was induced on the early period, 2 hrs, after stimulation at a wide range of concentration, $1{\sim}500\;\mu/ml$. In addition, the fraction of Korean mistletoe from 80% saturated ammonium sulphate precipitation showed a significant activity to induce both cytokines from macrophage. The present study demonstrates that Korean mistletoe contains immunoregulatory factors responsible for stimulating murine macrophage to secrete IL-1 and $TNF-{\alpha}$ which play an important role in immune responses, and suggests that the activity of Korean mistletoe to induce two cytokines is functioned by a possible independent stimulation manner.

• Archives of Pharmacal Research
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• v.28 no.11
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• pp.1257-1262
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• 2005

MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.